The approval was based on the results of the PACE trial, a multicenter, international, single-arm clinical trial of 449 patients with disease that was resistant or intolerant to prior tyrosine kinase inhibitor therapy. The primary endpoints were Major Cytogenetic Response (MCyR) for patients with CP-CML and Major Hematologic Response (MaHR) for patients with AP-CML, BP-CML or Ph+ALL. FDA required that the sponsor commit to submit 24-month follow-up data for all patients as a condition for the accelerated approval.

The efficacy results demonstrated a 54% MCyR rate in patients with CP-CML. Seventy percent of patients with CP-CML with T315I mutation achieved MCyR. The median duration of MCyR had not yet been reached at the time of analysis. For patients with AP-CML, BP-CML and Ph+ ALL, the MaHR rates were 52%, 31% and 41%, respectively. The median duration of MaHR in patients with AP-CML, BP-CML and Ph+ ALL was 9.5 months, 4.7 months and 3.2 months respectively.

Iclusig is being approved with a Boxed Warning alerting patients and healthcare professionals that arterial thrombosis and liver toxicity have occurred in Iclusig-treated patients. The most common side effects reported in the clinical trial include hypertension, rash, abdominal pain, fatigue, headache, dry skin, constipation, fever, joint pain, and nausea.

The recommended dose and schedule for ponatinib is 45 mg taken orally once daily with or without food.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).